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Diabetes Mellitus, Type 2Phase 1NCT03310749

An Assessment of Pharmacokinetic Gemigliptin and Metformin Interactions in Healthy Mexican Volunteers

A Phase 1 study testing Gemigliptin, Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day and Metformin in people with Diabetes Mellitus, Type 2, run by Stendhal Americas, S.A. at 1 site in Mexico.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is an open, randomized (randomization ratio: 1:1), multiple dose, three way, three period cross over study to assess the potential for drug drug interactions between gemigliptin (a DPP-IV inhibitor mainly metabolized by CYP3A4) and metformin in a sample of healthy Mexican volunteers, aimed to determine whether… Read more about this study

Who is it for?
Ages 20 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Gemigliptin, Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day and Metformin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteMexico
Study dates
15 Jan 2016to 3 May 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 45 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy male subjects at age between 20 and 45 at the screening test
  • Subjects with a body weight of 55kg or more but less than 90kg and a Body Mass Index (BMI) of between 18.0 or more but less than 27.0
  • BMI (kg/m2) = Weight (kg) / {Height (m)}2
  • Subjects who show the blood glucose level within the range of 70-125 mg/dL at the fasting plasma glucose (FPG) test conducted at screening
  • Subjects who fully understand this clinical trial after hearing a detailed explanation about it, make a decision to participate in it by his/her own free will, and sign an informed consent form to comply with the precautions

Who cannot join

  • Subjects who have a present condition or past history of any disease involving liver, kidney, nervous system, immune system, respiratory system, or endocrine system, hematologic and oncologic disease, cardiovascular disease, or psychiatric disorder (mood disorder, obsessive-compulsive disorder, etc.) (including subjects carrying hepatitis virus in case of liver disease)
  • Subjects with a past history of a gastrointestinal system disease (Crohn's disease, ulcer, acute or chronic pancreatitis, etc.) or a gastrointestinal system surgery (however, subjects with a history of appendectomy or hernioplasty are not excluded)
  • Subjects with a medical history of allergic reaction to drugs (aspirin, antibiotics, etc.) or clinically significant hypersensitivity reaction
  • Subjects who show one of the following results at screening test:
  • Exceeds 1.5 times the upper limit of the normal range of blood AST (SGOT) and ALT (SGPT)
  • The creatinine clearance calculated by Cockcroft-Gault equation is below 80 mL/min.
Show all 15Show fewer
  • QTc > 450 ms in ECG or clinically significant abnormal rhythm
  • In the vital signs measured in sitting position after a rest for 3 minutes or longer, subjects who showed a systolic blood pressure of ≤ 100 mmHg or ≥ 150 mmHg, or a diastolic blood pressure of ≤ 60 mmHg or ≥ 95 mmHg)
  • Subjects who have a past history of drug abuse or have shown a positive reaction to drugs that are used in abusive manner or cotinine at a urine drug screening
  • Subjects who have taken any ethical drug or an herbal medication within 2 weeks before the date of first administration or have taken any over-the-counter (OTC) drug or vitamin preparation within 1 week (however, they can be included as subjects if considered appropriate at the investigator's discretion judgment)
  • Subject who have already participated in other clinical trials within 2 months before the date of first drug administration
  • Subject who have had whole blood donation within 2 months or component blood donation within 1 month before the date of first drug administration, or transfusion in 1 month before the date of first drug administration
  • Subjects who have been drinking alcohol continuously (more than 21 units/week, 1 unit = 10 g of pure alcohol) or can't refrain from drinking alcohol during the clinical trial period
  • Smokers (however, if the subject stopped smoking more than 3 months before the date of the first drug administration, he/she can be selected as a subject)
  • 12) Subjects who have had grapefruit/ any food containing caffeine within 3 days before the date of the first drug administration

Trial locations and contacts

1 site in 1 country.

Mexico1 site

  • Unidad de Farmacología Clínica de la Facultad de Medicina de la Universidad Nacional Autónoma de México

    Nezahualcóyotl, State of Mexico, 57740

Other trials in Mexico

About this study

Official title: A Randomized, Open-label, Multiple Dosing, Three-way Crossover Clinical Trial to Investigate the Pharmacokinetic Drug-drug Interaction of Gemigliptin and Metformin After Oral Administration in Healthy Mexican Male Subjects

This is an open, randomized (randomization ratio: 1:1), multiple dose, three way, three period cross over study to assess the potential for drug drug interactions between gemigliptin (a DPP-IV inhibitor mainly metabolized by CYP3A4) and metformin in a sample of healthy Mexican volunteers, aimed to determine whether the observed lack of drug-drug interactions between gemigliptin and metformin in the Korean population is reproducible in an ethnically different population characterized by a significant difference in the frequency of CYP3A4 polymorphisms associated with decreased enzymatic activity, such as CYP3A4*1b, in comparison with Asian populations.

Read the detailed description

Consenting, eligible healthy adult subjects sequentially received either gemigliptin 50 mg q.d., metformin 1000 mg twice a day or gemigliptin 50 mg q.d. plus metformin 1000 mg twice a day during 3 consecutive 7 day treatment periods separated by two 5-day washout intervals, in accordance with a randomly assigned treatment sequence. Starting on the sixth treatment period day, participating subjects underwent safety assessments and repeated (24 hour) blood and urine sampling for pharmacokinetic analysis. All subjects attended to a post-study visit for final safety assessments within 8 days of study completion or early withdrawal.

Urine and plasma samples where processed to determine gemigliptin and metformin concentrations using validated analytical methods and pharmacokinetic profiles of both gemigliptin and metformin were obtained using a non-compartmental method; both the rate and degree of gemigliptin and metformin absorption resulting from their concomitant administration relative to the administration of each drug alone were assessed in search of potential pharmacokinetic interactions, Finally, a post hoc assessment of the degree and rate of the absorption of gemigliptin in the study population relative to those of a group of Korean subjects participating in phase I, repeated dose gemigliptin studies was conducted.

Being tested
Gemigliptin, Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day, Metformin
Keywords
Type 2 Diabetes Mellitus, DPP-IV inhibitor, Drug-Drug Interactions, Ethnicity
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GemigliptinDrug

    Also called Metformin, Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day

    A 7-day treatment period with gemigliptin 50 mg q.d., followed by a 5-day washout period; a 7 day treatment period with metformin 1000 mg twice a day followed by a 5-day washout period and a final 7-day treatment period with gemigliptin 50 mg q.d. + metformin 1000 mg twice a day

  • Gemigliptin 50 mg q.d. + metformin 1000 mg twice a dayDrug

    Also called Gemigliptin, Metformin

    A 7-day treatment period with gemigliptin 50 mg q.d. + metformin 1000 mg twice a day followed by a 5-day washout period; a 7-day treatment period with gemigliptin 50 mg q.d. followed by a 5-day washout period and a final 7-day treatment period with metformin 1000 mg twice a day

  • MetforminDrug

    Also called Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day, Gemigliptin

    A 7-day treatment period with 1000 mg metformin twice a day followed by a 5-day washout period; a 7-day treatment period with gemigliptin 50 mg q.d.+ metformin 1000 mg twice a day followed by a 5-day washout period and a final 7-day treatment period with gemigliptin 50 mg q.d.

Study groups in NCT03310749
Study groupRoleWhat they receive
Treatment sequence AOtherGemigliptin 50 mg q.d. during 7 days, metformin 1000 mg twice a day during 7 days and gemigliptin 50 mg q.d + metformin 1000 mg twice a day during 7 days.
Receives: Drug: Gemigliptin; Drug: Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Drug: Metformin
Treatment sequence BOtherGemigliptin 50 mg q.d + metformin 1000 mg twice a day during 7 days, gemigliptin 50 mg q.d. during 7 days, metformin 1000 mg twice a day during 7 days
Receives: Drug: Gemigliptin; Drug: Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Drug: Metformin
Treatment sequence COtherMetformin 1000 mg twice a day during 7 days, gemigliptin 50 mg q.d + metformin 1000 mg twice a day during 7 days, gemigliptin 50 mg q.d. during 7 days
Receives: Drug: Gemigliptin; Drug: Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Gemigliptin AUCτ,ss Geometric Mean Ratio (and 90%CI)

    AUCτ,ss Geometric Mean Ratio for gemigliptin when administered concomitanty with metformin (test) to its administration alone (reference)

    Measured: At steady state, on the sixth planned treatment day

Secondary outcomes (9)

  1. Gemigliptin Cmax,ss Geometric Mean Ratio (and 90%CI)

    Cmax,ss Geometric Mean Ratio for gemigliptin when administered concomitanty with metformin (test) to its administration alone (reference)

    Measured: At steady state, on the sixth planned treatment day

  2. Metformin AUCτ,ss Geometric Mean Ratio (and 90%CI)

    AUCτ,ss Geometric Mean Ratio for metformin when administered concomitanty with metformin (test) to its administration alone (reference)

    Measured: At steady state, on the sixth planned treatment day

  3. Metformin Cmax,ss Geometric Mean Ratio (and 90%CI)

    Cmax,ss Geometric Mean Ratio for metformin when administered concomitanty with metformin (test) to its administration alone (reference)

    Measured: At steady state, on the sixth planned treatment day

  4. Ctrough,ss

    Lowest plasma concentration prior to the next dose administration at steady state

    Measured: At steady state, on the sixth planned treatment day

  5. Aeτ,ss

    cumulative amount of drug excreted in the urine during a dosing interval

    Measured: At steady state, on the sixth planned treatment day

  6. CLss/F

    Apparent drug clearance

    Measured: At steady state, on the sixth planned treatment day

  7. CLR,ss

    Renal drug clearance

    Measured: At steady state, on the sixth planned treatment day

  8. MR

    Metabolic ratio

    Measured: At steady state, on the sixth planned treatment day

  9. Tmax

    Time to maximum plasma concentration at steady state

    Measured: At steady state, on the sixth planned treatment day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2017
  2. Study start15 Jan 2016
  3. Primary completion3 May 2016
  4. Study completion3 May 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Open, randomized, multiple dose, three way, three period, cross over, drug-drug interaction, safety and tolerability study
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03310749
Sponsor's protocol ID
LG/STDHL-DPCL009bis
Status last verified
Oct 2017
First submitted
13 Sep 2017
Last updated
16 Oct 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No formal plan has been established since at the time the study was conducted no consent was obtained from the subjects to share their individual data for research purposes different from those specifically defined in the study protocol

Publications

  • Kim SH, Jung E, Yoon MK, Kwon OH, Hwang DM, Kim DW, Kim J, Lee SM, Yim HJ. Pharmacological profiles of gemigliptin (LC15-0444), a novel dipeptidyl peptidase-4 inhibitor, in vitro and in vivo. Eur J Pharmacol. 2016 Oct 5;788:54-64. doi: 10.1016/j.ejphar.2016.06.016. Epub 2016 Jun 11.

    PubMed 27298192

  • Lim KS, Kim JR, Choi YJ, Shin KH, Kim KP, Hong JH, Cho JY, Shin HS, Yu KS, Shin SG, Kwon OH, Hwang DM, Kim JA, Jang IJ. Pharmacokinetics, pharmacodynamics, and tolerability of the dipeptidyl peptidase IV inhibitor LC15-0444 in healthy Korean men: a dose-block-randomized, double-blind, placebo-controlled, ascending single-dose, Phase I study. Clin Ther. 2008 Oct;30(10):1817-30. doi: 10.1016/j.clinthera.2008.10.013.

    PubMed 19014837

  • Lim KS, Cho JY, Kim BH, Kim JR, Kim HS, Kim DK, Kim SH, Yim HJ, Lee SH, Shin SG, Jang IJ, Yu KS. Pharmacokinetics and pharmacodynamics of LC15-0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers. Br J Clin Pharmacol. 2009 Dec;68(6):883-90. doi: 10.1111/j.1365-2125.2009.03376.x.

    PubMed 20002082

  • Kim N, Patrick L, Mair S, Stevens L, Ford G, Birks V, Lee SH. Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans. Xenobiotica. 2014 Jun;44(6):522-30. doi: 10.3109/00498254.2013.865856. Epub 2013 Dec 4.

    PubMed 24304170

  • Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007 Dec;116(3):496-526. doi: 10.1016/j.pharmthera.2007.09.004. Epub 2007 Oct 9.

    PubMed 18001838

  • Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013 Apr;138(1):103-41. doi: 10.1016/j.pharmthera.2012.12.007. Epub 2013 Jan 16.

    PubMed 23333322

  • Reyes-Hernandez OD, Lares-Asseff I, Sosa-Macias M, Vega L, Albores A, Elizondo G. A comparative study of CYP3A4 polymorphisms in Mexican Amerindian and Mestizo populations. Pharmacology. 2008;81(2):97-103. doi: 10.1159/000109983. Epub 2007 Oct 19.

    PubMed 17952011

  • Shin D, Cho YM, Lee S, Lim KS, Kim JA, Ahn JY, Cho JY, Lee H, Jang IJ, Yu KS. Pharmacokinetic and pharmacodynamic interaction between gemigliptin and metformin in healthy subjects. Clin Drug Investig. 2014 Jun;34(6):383-93. doi: 10.1007/s40261-014-0184-3.

    PubMed 24627290

  • Conde-Carmona I, Garcia-Medina S, Jimenez-Vargas JM, Martinez-Munoz A, Lee SH. Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: A Randomized, Open-label Study in Healthy Mexican Volunteers. Clin Ther. 2018 Oct;40(10):1729-1740. doi: 10.1016/j.clinthera.2018.08.015. Epub 2018 Sep 22.

    PubMed 30249366

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Gemigliptin, Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day and Metformin in people with Diabetes Mellitus, Type 2, run by Stendhal Americas, S.A. at 1 site in Mexico.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Gemigliptin AUCτ,ss Geometric Mean Ratio (and 90%CI) (time frame: At steady state, on the sixth planned treatment day). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03310749, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2017.

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